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"Smith, David L."
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Parliaments and politics during the Cromwellian protectorate
This is a detailed book-length study of the period of the Cromwellian Protectorate from December 1653 to its demise in May 1659.
Book
Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors
FoundationOne ® CDx (F1CDx) is a United States (US) Food and Drug Administration (FDA)-approved companion diagnostic test to identify patients who may benefit from treatment in accordance with the approved therapeutic product labeling for 28 drug therapies. F1CDx utilizes next-generation sequencing (NGS)-based comprehensive genomic profiling (CGP) technology to examine 324 cancer genes in solid tumors. F1CDx reports known and likely pathogenic short variants (SVs), copy number alterations (CNAs), and select rearrangements, as well as complex biomarkers including tumor mutational burden (TMB) and microsatellite instability (MSI), in addition to genomic loss of heterozygosity (gLOH) in ovarian cancer. CGP services can reduce the complexity of biomarker testing, enabling precision medicine to improve treatment decision-making and outcomes for cancer patients, but only if test results are reliable, accurate, and validated clinically and analytically to the highest standard available. The analyses presented herein demonstrate the extensive analytical and clinical validation supporting the F1CDx initial and subsequent FDA approvals to ensure high sensitivity, specificity, and reliability of the data reported. The analytical validation included several in-depth evaluations of F1CDx assay performance including limit of detection (LoD), limit of blank (LoB), precision, and orthogonal concordance for SVs (including base substitutions [SUBs] and insertions/deletions [INDELs]), CNAs (including amplifications and homozygous deletions), genomic rearrangements, and select complex biomarkers. The assay validation of >30,000 test results comprises a considerable and increasing body of evidence that supports the clinical utility of F1CDx to match patients with solid tumors to targeted therapies or immunotherapies based on their tumor’s genomic alterations and biomarkers. F1CDx meets the clinical needs of providers and patients to receive guideline-based biomarker testing, helping them keep pace with a rapidly evolving field of medicine.
Journal Article
The experience of revolution in Stuart Britain and Ireland : essays for John Morrill
\"This volume ranges widely across the social, religious and political history of revolution in seventeenth-century Britain and Ireland, from contemporary responses to the outbreak of war to the critique of the post-regicidal regimes; from royalist counsels to Lilburne's politics; and across the three Stuart kingdoms. However, all the essays engage with a central issue - the ways in which individuals experienced the crises of mid seventeenth-century Britain and Ireland and what that tells us about the nature of the Revolution as a whole. Responding in particular to three influential lines of interpretation - local, religious and British - the contributors, all leading specialists in the field, demonstrate that to comprehend the causes, trajectory and consequences of the Revolution we must understand it as a human and dynamic experience, as a process. This volume reveals how the understanding of these personal experiences can provide the basis on which to build up larger frameworks of interpretation\"-- Provided by publisher.
Book
The geography of imported malaria to non-endemic countries: a meta-analysis of nationally reported statistics
Malaria remains a problem for many countries classified as malaria free through cases imported from endemic regions. Imported cases to non-endemic countries often result in delays in diagnosis, are expensive to treat, and can sometimes cause secondary local transmission. The movement of malaria in endemic countries has also contributed to the spread of drug resistance and threatens long-term eradication goals. Here we focused on quantifying the international movements of malaria to improve our understanding of these phenomena and facilitate the design of mitigation strategies.
In this meta-analysis, we studied the database of publicly available nationally reported statistics on imported malaria in the past 10 years, covering more than 50 000 individual cases. We obtained data from 40 non-endemic countries and recorded the geographical variations.
Infection movements were strongly skewed towards a small number of high-traffic routes between 2005 and 2015, with the west Africa region accounting for 56% (13 947/24 941) of all imported cases to non-endemic countries with a reported travel destination, and France and the UK receiving the highest number of cases, with more than 4000 reported cases per year on average. Countries strongly linked by movements of imported cases are grouped by historical, language, and travel ties. There is strong spatial clustering of plasmodium species types.
The architecture of the air network, historical ties, demographics of travellers, and malaria endemicity contribute to highly heterogeneous patterns of numbers, routes, and species compositions of parasites transported. With global malaria eradication on the international agenda, malaria control altering local transmission, and the threat of drug resistance, understanding these patterns and their drivers is increasing in importance.
Bill & Melinda Gates Foundation, National Institutes of Health, UK Medical Research Council, UK Department for International Development, Wellcome Trust.
Journal Article
Hitting Hotspots: Spatial Targeting of Malaria for Control and Elimination
In more academic terms, an active focus of malaria transmission is a geographical area that supports malaria transmission, where the local Anopheles population sustains the basic reproductive rate (R0; average number of secondary infections arising in a susceptible population as a result of a single individual with malaria over the course of their malaria infection) at a level above 1 [16].\\n The most inclusive approach to clear infections in humans, including those that are present at densities below the detection limit of rapid diagnostic tests or microscopy [55] is to give mass drug administration (MDA) where a full therapeutic dose of drugs are administered to a population without prior screening. Because all age groups contribute to malaria transmission [57], VIMT may need to be administered to all age groups to see an impact.
Journal Article
The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017
Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to produce them.
For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted life-years (DALYs) for typhoid and paratyphoid fevers.
Globally, 14·3 million (95% uncertainty interval [UI] 12·5–16·3) cases of typhoid and paratyphoid fevers occurred in 2017, a 44·6% (42·2–47·0) decline from 25·9 million (22·0–29·9) in 1990. Age-standardised incidence rates declined by 54·9% (53·4–56·5), from 439·2 (376·7–507·7) per 100 000 person-years in 1990, to 197·8 (172·0–226·2) per 100 000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused 76·3% (71·8–80·5) of cases of enteric fever. We estimated a global case fatality of 0·95% (0·54–1·53) in 2017, with higher case fatality estimates among children and older adults, and among those living in lower-income countries. We therefore estimated 135·9 thousand (76·9–218·9) deaths from typhoid and paratyphoid fever globally in 2017, a 41·0% (33·6–48·3) decline from 230·5 thousand (131·2–372·6) in 1990. Overall, typhoid and paratyphoid fevers were responsible for 9·8 million (5·6–15·8) DALYs in 2017, down 43·0% (35·5–50·6) from 17·2 million (9·9–27·8) DALYs in 1990.
Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease.
Bill & Melinda Gates Foundation.
Journal Article
Ross, Macdonald, and a Theory for the Dynamics and Control of Mosquito-Transmitted Pathogens
Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different mathematical models, Macdonald a third, and various \"Ross-Macdonald\" mathematical models exist. Ross-Macdonald models are best defined by a consensus set of assumptions. The mathematical model is just one part of a theory for the dynamics and control of mosquito-transmitted pathogens that also includes epidemiological and entomological concepts and metrics for measuring transmission. All the basic elements of the theory had fallen into place by the end of the Global Malaria Eradication Programme (GMEP, 1955-1969) with the concept of vectorial capacity, methods for measuring key components of transmission by mosquitoes, and a quantitative theory of vector control. The Ross-Macdonald theory has since played a central role in development of research on mosquito-borne pathogen transmission and the development of strategies for mosquito-borne disease prevention.
Journal Article